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p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.

Kashuba E, Mattsson K, Klein G, Szekely L - Mol. Cancer (2003)

Bottom Line: The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites.Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden. Elena.Kashuba@mtc.ki.se

ABSTRACT

Background: p14ARF is a protein product of the alternative reading frame of the human INK4a locus. It functions as a tumor suppressor protein. p14ARF suppresses growth through p53-dependent and p53-independent pathways.

Results: p14ARF protein localizes primarily to the nucleoli. Here we show that in transfected cells p14ARF also appears in Hsp70 positive extranucleolar inclusions. The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.

Conclusion: Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites. Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.

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Related in: MedlinePlus

20S proteasomes are targeted to pBbae-p14ARF positive nuclear inclusions (hollow arrowheads) but not to the nucleoli (full arrowheads) in MCF7 cells. Green – p14ARF, red – 20S proteasome subunits, blue – DNA-staining.
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Figure 4: 20S proteasomes are targeted to pBbae-p14ARF positive nuclear inclusions (hollow arrowheads) but not to the nucleoli (full arrowheads) in MCF7 cells. Green – p14ARF, red – 20S proteasome subunits, blue – DNA-staining.

Mentions: In order to investigate whether the p14ARF nuclear inclusions could be targets of the degradation pathway, we have stained the transfected cells for the 20S core subunit of the proteasomes. The 20S subunits of the proteasomes were localized mainly to the cytoplasm of MCF7 cells. When p14ARF was expressed in cells, the 20S core subunits of the proteasomes were targeted to the nucleus and co-localized with p14ARF in the extra-nucleolar inclusions (Figure 4). Remarkably, the proteasomes were not associated with p14ARF when it was present in the nucleoli.


p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.

Kashuba E, Mattsson K, Klein G, Szekely L - Mol. Cancer (2003)

20S proteasomes are targeted to pBbae-p14ARF positive nuclear inclusions (hollow arrowheads) but not to the nucleoli (full arrowheads) in MCF7 cells. Green – p14ARF, red – 20S proteasome subunits, blue – DNA-staining.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153488&req=5

Figure 4: 20S proteasomes are targeted to pBbae-p14ARF positive nuclear inclusions (hollow arrowheads) but not to the nucleoli (full arrowheads) in MCF7 cells. Green – p14ARF, red – 20S proteasome subunits, blue – DNA-staining.
Mentions: In order to investigate whether the p14ARF nuclear inclusions could be targets of the degradation pathway, we have stained the transfected cells for the 20S core subunit of the proteasomes. The 20S subunits of the proteasomes were localized mainly to the cytoplasm of MCF7 cells. When p14ARF was expressed in cells, the 20S core subunits of the proteasomes were targeted to the nucleus and co-localized with p14ARF in the extra-nucleolar inclusions (Figure 4). Remarkably, the proteasomes were not associated with p14ARF when it was present in the nucleoli.

Bottom Line: The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites.Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden. Elena.Kashuba@mtc.ki.se

ABSTRACT

Background: p14ARF is a protein product of the alternative reading frame of the human INK4a locus. It functions as a tumor suppressor protein. p14ARF suppresses growth through p53-dependent and p53-independent pathways.

Results: p14ARF protein localizes primarily to the nucleoli. Here we show that in transfected cells p14ARF also appears in Hsp70 positive extranucleolar inclusions. The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.

Conclusion: Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites. Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.

Show MeSH
Related in: MedlinePlus